The present invention relates to a device for transdermal or transmucosal administration of drugs using iontophoresis, and particularly to a device to deliver drugs such as physiological active substances via the skin or mucosa such as the oral cavity and nasal cavity into a body using the principle of iontophoresis in the medical field.
Ointments, patches, or the like for transdermal and transmucosal administration, in addition to injections, oral preparations, and suppositories have conventionally been subjected to research and development as dosage forms of drugs such as physiological active substances. Transdermal and transmucosal administration has various advantages over the other administration methods, such as easiness in administration, maintenance of drug concentrations in blood, and avoidance of gastrointestinal adverse drug reactions. By transdermal and transmucosal administration, however, drugs are generally not absorbed well, and there are problems in absorption time and amount especially for drugs having a high molecular weight.
Various research and development efforts have been made on absorption-enhancing methods to increase drug absorption from the skin and mucosa. These methods include chemical enhancing methods using absorption-enhancing as well as physical enhancing methods using iontophoresis, phonophoresis, electrophoresis, or the like. Among these, in the case of iontophoresis, a drug is administered into a body via the skin or mucosa by applying voltage to the skin or mucosa to make an ionic drug migrate electrically.
Methods for energization applied for iontophoresis include direct current type energization, pulse type energization, and pulse depolarized type energization. Among these, pulse depolarized type energization has such advantages that it is excellent in terms of drug permeability over the direct current type and pulse type energization methods and that it gives only weak irritation on the skin and mucosa even applying a large electric current. The pulse depolarized type energization is described in, for example, Japanese Patent Laid-Open Publication No. 60-156475.
Since the pulse depolarized energization has the above-mentioned advantages, the method is quite useful for a device for iontophoresis. The present inventors faced a new problem, however, while we attempted practical application of a device, especially to obtain a small and portable device using this energization method. The problem is that the pulse depolarized energization consumes more electric power than the direct current type and pulse type energization methods. It is difficult to realize a reduction in device size and to obtain a portable device without solving this problem.
Therefore, it is an object of the present invention to provide a transdermal or transmucosal drug delivery device excellent in terms of drug permeability and skin irritability and capable of reducing electric power consumption.
The above objective can be accomplished by a transdermal or transmucosal drug delivery device configured so as to combine the pulse depolarized type energization (pulse depolarized direct current type energization) and at least one of direct current type energization and pulse type energization (pulse direct current type energization).
The combined energization was experimentally found by the present inventors, and any combination of the pulse depolarized type energization with other energization methods has not been attempted yet. It has been generally considered that such a combination that a part of the pulse depolarized type energization is replaced by other energization methods may reduce electric power consumption, but advantages in terms of drug permeability and skin irritability may also be reduced. However, experiments by the present inventors revealed that the above combinations of energization methods can drastically reduce electric power consumption with maintaining the effects in terms of drug permeability and skin irritability equally or at some degree. Then, repeated implementations of energization of these combinations could provide a greater effect. The details of the combined energization are determined by external setting of a device or based on the internal storage information.
Now, the direct current type energization supplies a predetermined direct current between electrodes, and the pulse type energization supplies predetermined repetitive pulses between electrodes. Although the pulse depolarized type energization supplies predetermined repetitive pulses between electrodes, like the pulse type energization, a residual charge is forced to be discharged during a pulse-resting phase, unlike the pulse type energization. These energization patterns can be provided by an energization pattern controller that generates a combined output comprising pulse depolarized output and at least one of direct current output and pulse output.